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Prior to meeting Blackie Lawless and Randy Piper, and joining W.A.S.P., Holmes played guitar with Los Angeles bands Buster Savage, LAX, and Slave. Holmes joined W.A.S.P. in 1982, and remained with the group until 1990. In 1996 Holmes rejoined W.A.S.P., and remained lead guitarist until 2001. Holmes has not played with W.A.S.P. since.

Holmes was contacted by friend and former bandmate Randy Piper to join Piper's new project, Animal. Holmes quickly relocated to Ohio to prepare for Animal's upcoming "900 lb Steam" tour. The tour was considered successful, and after its conclusion, Animal recorded tracks for a new album.

After Holmes returned to Los Angeles in late 2003, he began working with several Southern California-based metal groups, producing and contributing guitar tracks. In 2007, Holmes was involved with the filming of a Randy Rhoads documentary directed by Peter M. Margolis, which has yet to be released. Holmes appears briefly in a 2009 episode of VH1's Rock Docs, "Do It For The Band: The Women of Sunset Strip." In the Summer of 2009 Holmes released Secret Society's "Death by Misadventure."

On November 26, 2012, Chris released his first album solo Nothing to Lose and decided to produce, manage and distribute it himself along with his wife. After the success of his first Album, Chris started recording his second solo album, Shitting Bricks. The release date is yet to be confirmed.

While a member of W.A.S.P., Holmes participated in the filming of the documentary film, The Decline of Western Civilization Part II: The Metal Years. The film included interviews with many well known heavy metal personalities of the era discussing their lifestyle and the metal scene in late 1980s Los Angeles.

Holmes' contribution to the 1988 documentary is perhaps the most memorable, as he was interviewed while floating in a swimming pool, fully clothed and visibly quite intoxicated while his mother sat poolside. The interview stood out in stark contrast to the more light-hearted and humorous interviews conducted by director Penelope Spheeris, which mostly portrayed rockers as good-natured, though often dimwitted or deluded, party animals. During the interview, Holmes smiled drunkenly at the camera, deeming himself "a full-blown alcoholic" and "a piece of crap" despite his band's success, and punctuated his remarks by guzzling from three bottles of vodka. At the end of the interview, Holmes upends a full bottle of Smirnoff over his head as he rolls out of his inflatable chair and into the water.

Chris Holmes has been married three times. First to Kaylen Rodgers in the late 1980s, then briefly to Lita Ford in the early 1990s. He is now married to Catherine Sarah Holmes, whom he wed in 2012. The couple currently reside in France.

Jackson Custom Rhoads (Black with brass hardware). Used in the movie "The Dungeonmaster." Returned after Chris was offered an endorsement from Jackson/Charvel.

Jackson/Charvel Custom parts Star (Yellow, completely beaten-up).

Jackson Custom Star (White with red blood splatter).

Jackson Custom Rhoads (Black with white bevels, "I'm A Animal" painted in white on the back of the neck).

Jackson Custom Rhoads (White pearl with black bevels, with "Fuck Off N Die" painted in red on the back of the neck. This guitar was later sent back to Jackson's custom shop after the wing broke to get the wing cut shorter, as well as the slimmer neck and zebra/lion graphic added). Sold on eBay, currently residing in Finland.

Ibanez Destroyer (Red). In an interview, Holmes said that this guitar was borrowed by Eddie Van Halen for the recording of the Women and Children First album. The guitar can be seen in the Neil Zlozower "Women and Children First" Sunset Sound studio photographs. Eddie had a similar Ibanez Destroyer that he modified after recording Van Halen into the Shark Destroyer. Eddie did not like the tone after the modification so he borrowed Chris Holmes's Ibanez Destroyer. Holmes' Red Ibanez Destroyer is distinctive as it was modified to have only a single volume control whereas usually there are 2 volume and 1 tone control. The Red Ibanez Destroyer is now in the possession of The Tone Zone's Doug Anderson as part of his collection of Van Halen memorabilia often referred to as "The Van Halen Museum".[1][2]